{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T02:46:07Z","timestamp":1785033967192,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T00:00:00Z","timestamp":1622592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K18793"],"award-info":[{"award-number":["16K18793"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ohyama Health Foundation, Inc.","award":["None"],"award-info":[{"award-number":["None"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>African trypanosomes cause diseases in humans and livestock. Human African trypanosomiasis is caused by Trypanosoma brucei rhodesiense and T. b. gambiense. Animal trypanosomoses have major effects on livestock production and the economy in developing countries, with disease management depending mainly on chemotherapy. Moreover, only few drugs are available and these have adverse effects on patients, are costly, show poor accessibility, and parasites develop drug resistance to them. Therefore, novel trypanocidal drugs are urgently needed. Here, the effects of synthesized nitrofurantoin analogs were evaluated against six species\/strains of animal and human trypanosomes, and the treatment efficacy of the selected compounds was assessed in vivo. Analogs 11 and 12, containing 11- and 12-carbon aliphatic chains, respectively, showed the highest trypanocidal activity (IC50 &lt; 0.34 \u00b5M) and the lowest cytotoxicity (IC50 &gt; 246.02 \u00b5M) in vitro. Structure-activity relationship analysis suggested that the trypanocidal activity and cytotoxicity were related to the number of carbons in the aliphatic chain and electronegativity. In vivo experiments, involving oral treatment with nitrofurantoin, showed partial efficacy, whereas the selected analogs showed no treatment efficacy. These results indicate that nitrofurantoin analogs with high hydrophilicity are required for in vivo assessment to determine if they are promising leads for developing trypanocidal drugs.<\/jats:p>","DOI":"10.3390\/molecules26113372","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T21:23:41Z","timestamp":1622669021000},"page":"3372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["In Vitro and In Vivo Trypanocidal Efficacy of Synthesized Nitrofurantoin Analogs"],"prefix":"10.3390","volume":"26","author":[{"given":"Linous","family":"Munsimbwe","sequence":"first","affiliation":[{"name":"Ministry of Fisheries and Livestock, Department of Veterinary Services, Mulungushi House, P.O. Box 50600, Ridgeway, Lusaka 15100, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7787-9506","authenticated-orcid":false,"given":"Anna","family":"Seetsi","sequence":"additional","affiliation":[{"name":"Unit for Environmental Science and Management, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom 2531, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boniface","family":"Namangala","sequence":"additional","affiliation":[{"name":"Department of Paraclinical Studies, School of Veterinary Medicine, University of Zambia, P.O. Box 32379, Lusaka 10101, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"N\u2019Da","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Pharmaceutical Sciences (PHARMACEN), North-West University, Potchefstroom 2520, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Inoue","sequence":"additional","affiliation":[{"name":"OIE Reference Laboratory for Surra, National Research Centre for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Suganuma","sequence":"additional","affiliation":[{"name":"Research Center for Global Agromedicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/S0140-6736(17)31510-6","article-title":"Human African trypanosomiasis","volume":"390","author":"Cecchi","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s40249-017-0363-6","article-title":"Estimating the economic and social consequences for patients diagnosed with human African trypanosomiasis in Muchinga, Lusaka and Eastern Provinces of Zambia (2004\u20132014)","volume":"6","author":"Mwiinde","year":"2017","journal-title":"Infect. 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